DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 2, 4-12, 14, 15 and 17 are pending in this application.
Election/Restrictions
Applicant’s election of Group II (Claims 4-10) in the reply filed on 10/21/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 2, 11, 12, 15 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse.
Claims 4-10 were examined on their merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The use of the terms ALEXA-FLUOR™, CELLSCALE™ and SPACECLAIM™, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Claim 4 recites, “A bench-top model of atherosclerosis”. This has been construed as a non-structural intended use which will be evaluated only insofar as it provides a structural difference between the claimed invention and the prior art. See the MPEP at 2111.02, I and II.
Claim 6 has been construed under product-by-process consistent with the MPEP at 2113, I., wherein the product “(TEBV) comprising cells, an acellular tissue matrix and a hydrogel” is made by the process “comprising: selecting a group of cells, selecting an acellular tissue matrix and a hydrogel, and co-culturing the group of cells with the acellular tissue matrix and the hydrogel in a container”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4-10 are rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “bench-top” in claim 4 is a relative term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See the MPEP at 2173.05(b), II. which states:
A claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship between the limitation and the object is not sufficiently defined. That is, where the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite. See, e.g., Ex parte Miyazaki, 89 USPQ2d 1207 (Bd. Pat. App. & Inter. 2008)
In Brummer, the Board held that a limitation in a claim to a bicycle that recited "said front and rear wheels so spaced as to give a wheelbase that is between 58 percent and 75 percent of the height of the rider that the bicycle was designed for" was indefinite because the relationship of parts was not based on any known standard for sizing a bicycle to a rider, but on a rider of unspecified build. Brummer, 12 USPQ2d at 1655
For purposes of examination the Examiner has interpreted the limitation as any in vitro experimental model. Claims 5-10 are rejected as being dependent upon rejected Claim 4.
. Claim 4 recites, “utilizes tissue engineered blood vessel (TEBV)”, the limitation is indefinite because it merely claims a use without any active, positive steps delimiting how this use is actually practiced. See the MPEP 2173.05(q), I. Claims 5-10 are rejected as being dependent on Claim 4.
Claim 5 is rejected because of the parenthetical recitations of “early stage” and “late stage”. It is unclear if the terms are limiting embodiments, for example “early stage” does not appear to further define the process of “application of oxidized lipoprotein (oxLDLs)” because the term is also used after “followed by macrophage induction”.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 4 is rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Wada et al. (2000), cited in the IDS.
Wada et al. teaches a tissue engineered in vitro model of atherosclerosis of an arterial wall reconstruction model of Smooth Muscle Cells and Endothelial cells (Pg. 740, Abstract and Pg. 741, Fig. 1), and reading on Claim 4.
Claims 4 and 6-10 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Patel et al. (05/31/2021), cited in the IDS.
Patel et al. teaches a tissue engineered blood vessel (TEBV) comprising a group of cells (human dermal fibroblasts), an acellular (Pg. 1, Abstract) tissue matrix (ALLODERM™) and a fibrin hydrogel (Pg. 5, Fig. 1), and reading on Claims 4, 6 and 7;
wherein the hydrogel comprises ascorbic acid and TGF-β (Pg. 2, Lines 55-61), and reading on Claim 8;
a 6 mm diameter supporting post contacting the cells, hydrogel and acellular tissue matrix (Pg. 5, Fig. 1 and Pg. 2, Lines 47-53), reading on Claims 9 and 10.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 4-10 are rejected under 35 U.S.C. § 103 as being unpatentable over Patel et al. (05/31/2021), cited in the IDS, as applied to Claims 4 and 6-10 above, and further in view of Zhang et al. (2020) and Jahnen-Dechent et al. (US 2014/0377874 A1).
The teachings of Patel et al. were discussed above.
Patel et al. did not teach a method in which the stages of atherosclerosis are induced by application of oxidized LDLs followed by macrophage induction and induction using calcified protein particles, as required by Claim 5.
Zhang et al. teaches an in vitro TEBV model of early stage atherosclerosis which can identify the role of drugs on specific vascular functions that cannot be assessed in vivo (Pg. 1, Abstract) by application of modified LDL which induce macrophages (Pg. 3, Fig. 1a(ii) and wherein LDL can be modified by oxidation, acetylation and enzymatic modification (Pg. 5, Lines 6-7).
Jahnen-Dechent et al. teaches that that the most common form of calcification is atherosclerosis (Pg. 1, Paragraph [0006]), that cardiovascular calcification is the formation of one or more plaques localized in one or more blood vessels which may be characterized by the incorporation of low-density lipoprotein (LDL) and/or white blood cells, especially macrophages that have taken up oxidized low-density lipoprotein (LDL) which may lead to atherosclerosis (Pg. 2, Paragraph [0026]) and wherein calcification is any deposition and/or precipitation of poorly soluble or insoluble calcium salts and/or the formation of calciprotein particles (CPPs) in vivo and in vitro (Pg. 2, Paragraph [0022]).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the in vitro TEBV model of Patel et al. by application of modified (oxidized) LDL which induce macrophages as in the early stage model of atherosclerosis of Zhang et al. because this would provide an in vitro atherosclerosis model using simulated blood vessels. Those of ordinary skill in the art would have been motivated to make this modification in order to assess drug effects which cannot be tested in vivo. There would have been a reasonable expectation of success in making this modification because both Patel and Zhang are drawn to the same field of endeavor, that is, in vitro TEBV models.
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the in vitro TEBV model of atherosclerosis of Patel et al. and Zhang et al. with the induction of calcification with CPPs as taught by Jahnen-Dechent et al. because this would provide a further parameter in the pathology of atherosclerosis, the calcification (plaque formation) in the in vitro blood vessel model of atherosclerosis. Those of ordinary skill in the art would have been motivated to make this modification in order to prepare an in vitro model of atherosclerosis which more closely resembles the in vivo disease. There would have been a reasonable expectation of success in making this modification because both Patel and Zhang are drawn to the same field of endeavor, that is, in vitro TEBV models, Zhang teaches an in vitro TEBV model of atherosclerosis and Jahnen-Dechent et al. teaches that CPP mediate blood vessel calcification commonly found in atherosclerosis.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 11/10/2025